The last several decades have witnessed an onslaught of deadly pathogens around the globe. A broad array of human pathogens exists, including various microbes such as bacteria, protozoa, viruses, algae, and fungi. The innate capacity to respond to selective pressures has driven the evolution of microbes and enabled them to adapt to complex and variable environments. It is perhaps no surprise, then, that infectious microbes have readily evolved mechanisms to evade our attempts to destroy them with synthetic or natural anti-microbial compounds.
The fact that microbes develop resistance at a rate that far exceeds development of new therapeutics arguably poses the single most serious public health threat in this century in both developing and developed nations. There is no denying that anti-microbial strategies have met with spectacular success over the last century. For example, antibacterial and antiviral drugs directed at targets within the pathogen have been used to save countless lives. But it is becoming increasingly evident that such success is not sustainable. To counter these drugs, bacteria and viral pathogens have evolved sophisticated mechanisms to inactivate these compounds. Examples include the pan-drug resistant strains of Staphylococcus aureus, Klebsiella pneumonia, and Pseudomonas aerginosa, and Mycobacterium tuberculosis (TB) among bacteria and human immunodeficiency virus (HIV) among viruses.
More worrisome still is the lack of effort on the part of pharmaceutical companies (big or small) to pursue development of new antimicrobials. Efforts to develop new antibiotics by the pharmaceutical industry by large-scale screens of chemical libraries that inhibit growth have largely failed, and new tetracycline and sulfanilamide analogs will likely engender resistance and will quickly be rendered useless. The resistance problem is compounded further by indiscriminate and inappropriate use of antibiotics and antiviral compounds without compliance measures or public health policies to reduce disease burden. With the astounding costs of clinical trials (e.g., approximately $400M to bring new tetracyclines to the market for an expected revenue of $100M), the failure to control generic sales, and the capacity to generate substantial revenues from medications for chronic illnesses there is little if any financial incentive for big pharmaceutical companies to even develop new antibiotics, and small biotechnology companies simply do not have the resources.
Even with the current level of effort there is cause for concern. Of the new drugs under development, most, if not all, will likely engender resistance quickly upon release (e.g., folate biosynthesis inhibitor Icalprim). The search for novel antiviral compounds has been somewhat more successful and largely motivated by the HIV pandemic, but drugs have been developed principally against viral targets, and mutation rates among viruses still outpaces new development. One positive development has been vaccines, which are promising for some bacterial and viral illnesses. But vaccines are not successful in all cases (e.g., in young children), and adequate resources have not been made available.
There is therefore an urgent need to develop compounds and methods effective for the prevention and treatment of pathogenic infection.